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Inflammation

, Volume 42, Issue 6, pp 1925–1938 | Cite as

Upregulated MiR-9-5p Protects Against Inflammatory Response in Rats with Deep Vein Thrombosis via Inhibition of NF-κB p50

  • Minghui Ou
  • Yunfeng Zhang
  • Shichao Cui
  • Shibo Zhao
  • Jie TuEmail author
ORIGINAL ARTICLE
  • 91 Downloads

Abstract

Recently, microRNAs (miRNAs) have been demonstrated to play important roles in the cardiovascular system, including heart, blood vessels, plasma, and vascular diseases. Deep vein thrombosis (DVT) refers to the formation of blood clot in the deep veins of the human body and is a common peripheral vascular disease. Herein, we explored the mechanism of miR-9-5p in DVT through nuclear factor-κB (NF-κB). The expression of miR-9-5p in DVT rats was measured through the establishment of DVT rat models, followed by the alteration of miR-9-5p and NF-κB p50 in rats through the injection of constructed lentiviral vectors so as to explore the role of miR-9-5p and NF-κB p50 expression in rats. Next, the expression of NF-κB p50 and levels of inflammation-related factors plasminogen activator inhibitor-1 (PAI-1), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and interleukin-8 (IL-8) were measured after the injection with lentiviral vectors, followed by the assessment of platelet aggregation and TXB2 content. MiR-9-5p was found to be downregulated in DVT rats. Through dual luciferase reporter gene assay, NF-κB p50 was verified as the target gene of miR-9-5p and miR-9-5p could negatively regulate NF-κB p50. MiR-9-5p over-expression decreased the levels of PAI-1, TNF-α, IL-6, and IL-8 and platelet aggregation as well as TXB2 content, thus inhibiting thrombosis. Meanwhile, over-expressed NF-κB p50 could reverse the anti-inflammatory or anti-thrombotic effect of miR-9-5p. In summary, miR-9-5p over-expression can suppress the NF-κB signaling pathway through p50 downregulation, thus alleviating inflammation and thrombosis in DVT rats. MiR-9-5p could serve as a potential therapeutic target for DVT.

KEY WORDS

deep vein thrombosis microRNA-9-5p inhibition transcription factor nuclear factor-κB p50 inflammatory response thrombosis 

Notes

Acknowledgments

We would like to give our sincere appreciation to the reviewers for their helpful comments on this article.

Funding

This study was supported by General Program of National Natural Science Foundation (No. 81871187), Regional Projects of National Natural Science Foundation (No. 81460239), and Natural Science Foundation Project of Ningxia Hui Autonomous Region (No. NZ17195).

Compliance with Ethical Standards

Ethical Approval

All animal experiments were carried out in accordance with the principles and procedures of the National Institute of Animal Health Care Guidelines and approved by the Animal Ethics Committee of Qingdao Municipal Hospital.

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

10753_2019_1031_Fig7_ESM.png (860 kb)
Supplementary Figure 1

Recombinant expression vectors. A, lentivirus expression vector pMDLg/pRRE; B, pGL3-Basic vector; C, pMIR-reporter vector (PNG 859 kb)

10753_2019_1031_MOESM1_ESM.eps (2.2 mb)
High resolution image (EPS 2227 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Minghui Ou
    • 1
  • Yunfeng Zhang
    • 2
  • Shichao Cui
    • 1
  • Shibo Zhao
    • 1
  • Jie Tu
    • 3
    Email author
  1. 1.Department of Vascular SurgeryQingdao Municipal HospitalQingdaoPeople’s Republic of China
  2. 2.Department of OrthopedicsQingdao Municipal HospitalQingdaoPeople’s Republic of China
  3. 3.Science and Education DepartmentQingdao Municipal HospitalQingdaoPeople’s Republic of China

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